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BMC Research Notes Dec 2023Prior studies have shown controversial results on the vertical transmission of BK virus (BKV). The present study aimed to assess the possibility of BKV vertical...
OBJECTIVE
Prior studies have shown controversial results on the vertical transmission of BK virus (BKV). The present study aimed to assess the possibility of BKV vertical transmission from mother to fetus in the product of conception (embryo, fetuses, and/or placentas) over the three stages of pregnancy.
RESULTS
Of the 26 placental studied tissues, 6 were in the first trimester, and none of which were positive. Only one out of the 13 (7.7%) placental materials in the second trimester was positive. Only one out of 7 (14%) placental materials of the third trimester was positive. There were cases that no virus was detected in their placental but BKV was detected in their other tissues. Among 26 conceptuses, 17 (65%) were negative for BKV and 9 (34.6%) were positive, 7/13 (54%) were positive in the second, and 2/7 (29%) were positive in the third trimester fetuses. BKV was most frequently detected in the liver (eight cases), heart (three cases), and placenta (2 cases). There were cases that no virus was detected in their placental but BKV was detected in their other tissues.
Topics: Pregnancy; Female; Humans; Placenta; Pregnancy Trimester, Third; BK Virus; Pregnancy Complications, Infectious; Fetus; Polyomavirus Infections
PubMed: 38082354
DOI: 10.1186/s13104-023-06643-1 -
Clinical Microbiology Reviews Apr 2017BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal... (Review)
Review
BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN. Antiviral immunity plays a crucial role in controlling BKV replication, and our increasing knowledge about host-virus interactions has led to the development of improved diagnostic tools and clinical management strategies. Currently, there are no effective antiviral agents for BKV infection, and the mainstay of managing reactivation is reduction of immunosuppression. Development of immune-based therapies to combat BKV may provide new and exciting opportunities for the successful treatment of BKV-associated complications.
Topics: Antiviral Agents; BK Virus; Humans; Immunocompromised Host; Polyomavirus Infections; Tumor Virus Infections
PubMed: 28298471
DOI: 10.1128/CMR.00074-16 -
Viruses Jun 2019BK polyomavirus (BKV) reactivates from latency after immunosuppression in renal transplant patients, resulting in BKV-associated nephropathy (BKVAN). BKVAN has emerged...
BACKGROUND
BK polyomavirus (BKV) reactivates from latency after immunosuppression in renal transplant patients, resulting in BKV-associated nephropathy (BKVAN). BKVAN has emerged as an important cause of graft dysfunction and graft loss among transplant patients. BKV infection in kidney transplant patients has increased over recent decades which correlates with the use of more potent immunosuppressive therapies. BKV infection of the Glomerular Vascular Unit (GVU) consisting of podocytes, mesangial cells, and glomerular endothelial cells could lead to glomerular inflammation and contribute to renal fibrosis. The effects of BKV on GVU infectivity have not been reported.
METHODS
We infected GVU cells with the Dunlop strain of BKV. Viral infectivity was analyzed by microscopy, immunofluorescence, Western blot analysis, and quantitative RT-PCR (qRT-PCR). The expression of specific proinflammatory cytokines induced by BKV was analyzed by qRT-PCR.
RESULTS
BKV infection of podocytes, mesangial cells, and glomerular endothelial cells was confirmed by qRT-PCR and positive staining with antibodies to the BKV VP1 major capsid protein, or the SV40 Large T-Antigen. The increased transcriptional expression of interferon gamma-induced protein 10 (CXCL10/IP-10) and interferon beta (IFNβ) was detected in podocytes and mesangial cells at 96 h post-infection.
CONCLUSIONS
All cellular components of the GVU are permissive for BKV replication. Cytopathic effects induced by BKV in podocytes and glomerular endothelial cells and the expression of CXCL10 and IFNβ genes by podocytes and mesangial cells may together contribute to glomerular inflammation and cytopathology in BKVAN.
Topics: BK Virus; Cytokines; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Polyomavirus Infections; Postoperative Complications; Virus Activation; Virus Replication
PubMed: 31252545
DOI: 10.3390/v11070583 -
Experimental and Clinical... Jan 2019The prevalence of BK-induced nephritis in renal transplant recipients is estimated to be 1% to 10%; the rate of graft loss within 1 year is 30% to 65%. We conducted this...
OBJECTIVES
The prevalence of BK-induced nephritis in renal transplant recipients is estimated to be 1% to 10%; the rate of graft loss within 1 year is 30% to 65%. We conducted this study to evaluate screening of BK virus in blood and/or urine among renal transplant recipients and to assess the effects of different therapeutic modalities in renal transplant recipients with BK nephropathy.
MATERIALS AND METHODS
Kidney transplant recipients were screened at the time of transplant and then at 1, 2, 3, 6, 9, 12, 18, and 24 months posttransplant. Fiftynine patients were diagnosed with BK virus viremia. Patients were divided into 2 groups according to treatment: group 1 (n = 29) received an active treatment and group 2 (n = 30) received minimized immunosuppression.
RESULTS
Most patients required graft biopsies to confirm diagnosis (86.2% in group 1 vs 50% in group 2; P = .03). Both groups were comparable regarding demographic data. Initial posttransplant graft function was significantly better in group 1 (P = .017); ultimately, there was no significant difference between both groups regarding graft survival (P= .51). Fifty percent of patients had biopsy-proven acute T-cell-mediated rejection before BK virus-associated nephropathy diagnosis (significantly higher in group 1). Serum creatinine levels were significantly better in group 2 at 3, 4, and 5 years after BK nephropathy (P = .001, .017, and .003, respectively).
CONCLUSIONS
The prevalence of BK nephropathy in our renal transplant recipients was 5.9% with a rate of graft loss ranging from 43% to 51%. Regular screening, less intensive immunosuppressive therapy, and early intervention by reduction of immunosuppressive medications are advisable to obtain early diagnosis and to have better outcomes of BK virus-associated nephropathy with antiviral agents.
Topics: Antiviral Agents; BK Virus; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Kuwait; Opportunistic Infections; Polyomavirus Infections; Prevalence; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 30777529
DOI: 10.6002/ect.MESOT2018.O17 -
The Indian Journal of Medical Research Nov 2013Stem cell and organ transplantation are considered as the major advances of modern medicine. Unfortunately the success of transplantation is limited by its toxicity and... (Review)
Review
Stem cell and organ transplantation are considered as the major advances of modern medicine. Unfortunately the success of transplantation is limited by its toxicity and infectious complications as a result of profound immunosuppression. Viral infections are an extremely common and predictable problem in these patients. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. Over the last few years, there is increasing evidence that cellular immune therapies can reverse the outgrowth of haematological malignancies and can also provide therapeutic benefit against lethal viral infections. While the expansion and adoptive transfer of virus-specific T-cells from the healthy donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Recent studies have demonstrated successful expansion of virus-specific T-cells from seropositive stem cell transplant recipients of a seronegative graft with active virus disease and the long term reconstitution of protective anti-viral immunity following their adoptive transfer back into the patients. Furthermore, this immunotherapeutic strategy has also been extended for multiple pathogens including cytomegalovirus, Epstein-Barr virus, adenovirus and BK polyoma-virus. This approach can be employed to rapidly expand multiple pathogens-specific T cells that can be used for adoptive immunotherapy. Finally, new assays to monitor T cell immunity have been developed which will allow to identify the high risk transplant patients who may develop virus-associated complications post-transplantation and can be given adoptive T cell therapy prophylactically.
Topics: Adenoviridae; Antiviral Agents; BK Virus; Cytomegalovirus; Herpesvirus 4, Human; Humans; Immunotherapy, Adoptive; Infections; Interferon-gamma; Organ Transplantation; Stem Cell Transplantation; T-Lymphocytes; Viral Load; Virus Diseases
PubMed: 24434332
DOI: No ID Found -
PeerJ 2023BK virus (BKV)-associated nephropathy (BKVN) is one of the leading causes of renal dysfunction and graft loss in renal transplant recipients. Early monitoring of BKV in...
BACKGROUND
BK virus (BKV)-associated nephropathy (BKVN) is one of the leading causes of renal dysfunction and graft loss in renal transplant recipients. Early monitoring of BKV in urine is crucial to minimize the deleterious effects caused by this virus on preservation of graft function.
METHODS
We report a simple, rapid, sensitive loop-mediated isothermal amplification (LAMP) assay using an HFman probe for detecting BKV in urine. To evaluate the performance of the assay, a comparison of the HFman probe-based LAMP (HF-LAMP) assay with two qPCR assays was performed using urine samples from 132 HIV-1 infected individuals. We further evaluated the performance of HF-LAMP directly using the urine samples from these HIV-1 infected individuals and 30 kidney transplant recipients without DNA extraction. Furthermore, we combined the HF-LAMP assay with a portable finger-driven microfluidic chip for point-of-care testing (POCT).
RESULTS
The assay has high specificity and sensitivity with a limit of detection (LOD) of 12 copies/reaction and can be completed within 30 min. When the DNA was extracted, the HF-LAMP assay showed an equivalent and potentially even higher sensitivity (93.5%) than the qPCR assays (74.2-87.1%) for 132 urine samples from HIV-1 infected individuals. The HF-LAMP assay can be applied in an extraction-free format and can be completed within 45 min using a simple heat block. Although some decreased performance was seen on urine samples from HIV-1 infected individuals, the sensitivity, specificity, and accuracy of the extraction-free BKV HF-LAMP assay were 95%, 100%, and 96.7% for 30 clinical urine samples from kidney transplant recipients, respectively.
CONCLUSION
The assay has high specificity and sensitivity. Combined with a portable finger-driven microfluidic chip for easy detection, this method shows great potential for POCT detection of BKV.
Topics: Humans; BK Virus; Point-of-Care Systems; Microfluidics; DNA, Viral; Polyomavirus Infections; Nephritis, Interstitial
PubMed: 36915661
DOI: 10.7717/peerj.14943 -
BMC Infectious Diseases Aug 2020BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from...
BACKGROUND
BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from reactivation of the latent and usually harmless BK virus (BK virus) due to immunosuppression and other factors including some that are unique to renal transplantation such as allograft injury. BKVAN is much rarer in non-renal solid organ transplantation, where data regarding diagnosis and management are extremely limited.
CASE PRESENTATION
We report a case of a 58-year-old man found to have worsening renal dysfunction nine months after bilateral sequential lung transplantation for chronic obstructive pulmonary disease (COPD). He had required methylprednisolone for acute allograft rejection but achieved good graft function. Urine microscopy and culture and renal ultrasound were normal. BK virus PCR was positive at high levels in urine and blood. Renal biopsy subsequently confirmed BKVAN. The patient progressed to end-stage renal failure requiring haemodialysis despite reduction in immunosuppression, including switching mycophenolate for everolimus, and the administration of intravenous immunoglobulin (IVIG).
CONCLUSIONS
This very rare case highlights the challenges presented by BK virus in the non-renal solid organ transplant population. Diagnosis can be difficult, especially given the heterogeneity with which BKV disease has been reported to present in such patients, and the optimal approach to management is unknown. Balancing reduction in immunosuppression against prevention of allograft rejection is delicate. Improved therapeutic options are clearly required.
Topics: BK Virus; DNA, Viral; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Lung Transplantation; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Polyomavirus Infections; Pulmonary Disease, Chronic Obstructive; Tumor Virus Infections
PubMed: 32795251
DOI: 10.1186/s12879-020-05292-0 -
Clinical & Developmental Immunology 2013JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct,... (Review)
Review
JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of the Polyomaviridae family that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host.
Topics: Antiviral Agents; BK Virus; Genome, Viral; Humans; Immune Evasion; Immune System; Immunocompromised Host; JC Virus; Phylogeny; Polyomaviridae; Polyomavirus Infections; RNA, Viral; Tumor Virus Infections; Virus Activation
PubMed: 23737811
DOI: 10.1155/2013/373579 -
American Journal of Transplantation :... Aug 2017Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are not available. We studied 206 biopsies (71 patients), followed 3.09 ± 1.46 years after...
Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are not available. We studied 206 biopsies (71 patients), followed 3.09 ± 1.46 years after immunosuppression reduction. The biopsy features (% immunostain for PyV large T ag + staining and inflammation ± acute rejection) were correlated with viral load dynamics and serum creatinine to define the clinicopathological status (PyVCPS). Incidence of acute rejection was 28% in the second biopsy and 50% subsequently (25% mixed T cell-mediated allograft rejection (TCMR) + antibody-mediated allograft rejection (AMR); rejection overall affected 38% of patients (>50% AMR). Graft loss was 15.4% (0.8-5.3 years after PyVAN); 76% had complete viral clearance (mean 28 weeks). The only predictors of graft loss were acute rejection (TCMR p = 0.008, any type p = 0.07), and increased "t" and "ci" in the second biopsy (p = 0.006 and 0.048). Higher peak viremia correlated with poorer viral clearance (p = 0.002). Presumptive and proven PyVAN had similar presentation, evolution, and outcome. Late PyVAN (>2 years, 9.8%) justifies BK viremia evaluation at any point with graft dysfunction and/or biopsy evaluation. This study describes the histological evolution of PyVAN and corresponding clinicopathological correlations. Although the pathological features overall reflect the viral and immunological interactions, the PyVAN course remains difficult to predict based on any single feature. Appropriate clinical management requires repeat biopsies and determination of the PyVCPS at relevant time points, for corresponding personalized immunosuppression adjustment.
Topics: Adult; Aged; Aged, 80 and over; BK Virus; Cohort Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Kidney Diseases; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Polyomavirus Infections; Postoperative Complications; Prognosis; Risk Factors; Transplantation, Homologous; Tumor Virus Infections; Viral Load; Viremia
PubMed: 28422412
DOI: 10.1111/ajt.14314 -
Iranian Journal of Kidney Diseases Nov 2022BK virus nephropathy (BKVN) is an important complication of kidney transplantation and kidney biopsy remains the gold standard for its diagnosis. Urine/serum polymerase...
INTRODUCTION
BK virus nephropathy (BKVN) is an important complication of kidney transplantation and kidney biopsy remains the gold standard for its diagnosis. Urine/serum polymerase chain reaction (PCR) is a more sensitive diagnostic method, although it has some potential limitations.
METHODS
This study enrolled all kidney transplant recipients who underwent kidney transplant biopsy, collected from three medical centers. Urine and serum PCR results of the patients were also collected from the molecular laboratories. The cut-off value for positive viral DNA load in serum and urine were > 104 and > 107 copies/mL, respectively. Sensitivity, specifity, positive and negative predictive values (PPV, NPV) and cut off values for PCR results were compared with pathologic diagnosis among laboratories.
RESULTS
Among 369 biopsy samples, 33 (8.9%) had definite diagnosis of BKVN. PCR results were available for 138 cases. Three patients with definite BKVN had negative PCR results. In 22 patients, PCR was positive without evidence of BKVN. The overall sensitivity, specificity, PPV and NPV of PCR for detecting BKVN, based on a unique cut-off value, were 88, 81, 51, and 97%; respectively. The overall accuracy of PCR in all laboratories was high (82 to 86%), however significant inter-laboratory differences in sensitivity and specificity was found . A 2-log difference in threshold value for positive results was observed in one laboratory.
CONCLUSION
PCR may show a significant variability between different laboratories. Interpretation of PCR results using a single cut-off value for all laboratories, may decrease the sensitivity for the diagnosis and screening of BKVN. DOI: 10.52547/ijkd.7143.
Topics: Humans; BK Virus; Iran; Kidney Transplantation; Transplant Recipients; Nephritis, Interstitial
PubMed: 36454033
DOI: No ID Found